Published online before print August 29, 2002, doi: 10.1161/01.ATV.0000035404.18281.37
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© 2002 American Heart Association, Inc.
Vascular Biology |
Increased Monocyte Adhesion to Aortic Endothelium in Rats With Hyperhomocysteinemia
Role of Chemokine and Adhesion Molecules
From the Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong Kong, China.
Correspondence to Dr Karmin O, MB, PhD, Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 2/F, Laboratory Block, New Medical Complex, 21 Sassoon Rd, Hong Kong, China. E-mail okarmin{at}hkucc.hku.hk
Objective— The stimulatory effect of homocysteine (Hcy) on monocyte chemoattractant protein (MCP)-1 expression in vitro has been suggested to play an important role in Hcy-mediated atherosclerosis. We investigated whether such a stimulatory effect occurs in vivo, leading to monocyte adhesion to the endothelium.
Methods and Results— Sprague-Dawley rats were divided into 4 groups. Hyperhomocysteinemia was induced in 1 group of rats after 4 weeks of a high-methionine diet (serum Hcy levels were 4- to 5-fold higher than levels in control rats). The number of ED-1–positive cells present on the surface of aortic endothelium was significantly elevated in hyperhomocysteinemic rats. There was a significant increase in the expression of MCP-1, vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in the endothelium. Antibodies recognizing MCP-1, VCAM-1, or E-selectin could abolish the enhanced monocyte binding to the aortic endothelium of hyperhomocysteinemic rats. Endothelium-dependent aortic relaxation was impaired in hyperhomocysteinemic rats.
Conclusions— These results suggest that in the absence of other known risk factors, hyperhomocysteinemia stimulates the expression of MCP-1, VCAM-1, and E-selectin in vivo, leading to increased monocyte adhesion to the aortic endothelium. Such an effect may contribute significantly to the development of atherosclerosis by facilitating monocyte/macrophage infiltration into the arterial wall.
Key Words: hyperhomocysteinemia • atherosclerosis • monocyte chemoattractant protein-1 • cytokines • monocytes
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